Abstract MP62: Fatty Acid Biomarkers of 15:0, 17:0 and <i>Trans</i> 16:1n-7 and Incident Coronary Heart Disease and Stroke: A Pooling Project of 15 Prospective Cohorts in the Fatty Acids and Outcomes Research Consortium
Authors: Andres V Ardisson Korat, Frank Qian, Vasanti Malik, Marcus Lehr, Fumiaki Imamura, Nathan Tintle, Markku Laakso, Rob van Dam, William Harris, Matti Marklund, Cecilia Samieri, MacKenzie Senn, Karin Leander, Nita Forouhi, Ulf Riserus, Kou-Liong Chien, Amelia Chen, Alexis Wood, Weihua Guan, Michael Y Tsai, Rachel Murphy, David S Siscovick, Rozenn Lemaitre, Dariush Mozaffarian, Qi Sun
Journal: Circulation (2023)

Introduction: Previous studies have reported inverse associations of circulating and tissue levels of pentadecanoic acid (15:0), heptadecanoic acid (17:0) and trans -palmitoleic acid ( trans 16:1n-7), which have been proposed as potential biomarkers of dairy fat intake, with risk of type-2 diabetes and certain cardiovascular outcomes. Hypothesis: We assessed the hypothesis that circulating and tissue levels of 15:0, 17:0, trans 16:1n-7 are inversely associated with risk of incident coronary heart disease (CHD) and stroke in a global consortium of prospective studies. Methods: We used data from 15 prospective cohorts in the Fatty Acids and Outcomes Research Consortium. We included adults (age≥18 years) who were free of cardiovascular diseases and had blood or adipose tissue measurements of 15:0, 17:0 or trans 16:1n-7. We used a harmonized analysis protocol with each exposure standardized to the interquintile range (IQR): difference between the 10 th and 90 th percentiles of each fatty acid to conduct new individual participant-level analyses. We harmonized covariate definitions across studies to include demographic, lifestyle and health variables, and levels of other fatty acids associated with CHD or stroke. We used inverse-variance meta-analysis to calculate the pooled relative risks (RR) and 95% confidence intervals (CI) for each outcome. We also calculated Spearman correlation coefficients between levels of each fatty acid exposure and potential dietary determinants of their levels (intakes of total, high-fat and low-fat dairy, meat from ruminant animals, fish and dietary fiber) among 6 studies with dietary data. Results and Conclusions: Among 34,187 participants, 5,790 incident CHD and 3,098 stroke cases were documented during a maximum follow-up of 23.3 years. We did not observe significant associations of any of the fatty acid biomarkers with risk of CHD or stroke. The pooled multivariate RR and 95% CI of CHD per IQR were 0.97 (0.92, 1.02) for 15:0, 0.97 (0.92, 1.02) for 17:0, 1.11 (0.97, 1.26) for trans 16:1n-7, and 0.98 (0.92, 1.04) for the sum of the fatty acids. The respective RR and 95% of stroke were 1.01 (0.93, 1.09) for 15:0, 0.91 (0.81, 1.03) for 17:0, 0.99 (0.83, 1.18) for trans 16:1n-7, and 0.93 (0.85, 1.04) for the summed fatty acids. Additionally, we did not observe significant heterogeneity by age, sex, race/ethnicity, world region, baseline hypertension status or lipid compartment. Circulating and tissue levels of 15:0, 17:0 and trans 16:1n-7 were weakly correlated with intakes of total or high-fat dairy (Spearman correlations [ r = 0.05 to 0.37]) but were not correlated with intakes of low-fat dairy, ruminant meat, fish or dietary fiber [ r = -0.08 to 0.09]. In conclusion, circulating and tissue levels of 15:0, 17:0, trans 16:1n-7 were not associated with risk of CHD or stroke. Our study suggests a limited role for these fatty acids in the etiology of cardiovascular disease.